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Andrew R Moore - One of the best experts on this subject based on the ideXlab platform.
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topical analgesics for acute and chronic pain in adults an overview of cochrane reviews
Cochrane Database of Systematic Reviews, 2017Co-Authors: Sheena Derry, Philip J Wiffen, Eija Kalso, Rae Frances Bell, Dominic Aldington, Tudor Phillips, Helen Gaskell, Andrew R MooreAbstract:Background Topical analgesic drugs are used for a variety of painful conditions. Some are acute, typically strains or sprains, tendinopathy, or muscle aches. Others are chronic, typically osteoarthritis of hand or knee, or neuropathic pain. Objectives To provide an overview of the analgesic efficacy and associated adverse events of topical analgesics (primarily nonsteroidal anti-inflammatory drugs (NSAIDs), salicylate Rubefacients, capsaicin, and lidocaine) applied to intact skin for the treatment of acute and chronic pain in adults. Methods We identified systematic reviews in acute and chronic pain published to February 2017 in the Cochrane Database of Systematic Reviews (the Cochrane Library). The primary outcome was at least 50% pain relief (participant-reported) at an appropriate duration. We extracted the number needed to treat for one additional beneficial outcome (NNT) for efficacy outcomes for each topical analgesic or formulation, and the number needed to treat for one additional harmful outcome (NNH) for adverse events. We also extracted information on withdrawals due to lack of efficacy or adverse events, systemic and local adverse events, and serious adverse events. We required information from at least 200 participants, in at least two studies. We judged that there was potential for publication bias if the addition of four studies of typical size (400 participants) with zero effect increased NNT compared with placebo to 10 (minimal clinical utility). We extracted GRADE assessment in the original papers, and made our own GRADE assessment. Main results Thirteen Cochrane Reviews (206 studies with around 30,700 participants) assessed the efficacy and harms from a range of topical analgesics applied to intact skin in a number of acute and chronic painful conditions. Reviews were overseen by several Review Groups, and concentrated on evidence comparing topical analgesic with topical placebo; comparisons of topical and oral analgesics were rare. For at least 50% pain relief, we considered evidence was moderate or high quality for several therapies, based on the underlying quality of studies and susceptibility to publication bias. In acute musculoskeletal pain (strains and sprains) with assessment at about seven days, therapies were diclofenac Emulgel (78% Emulgel, 20% placebo; 2 studies, 314 participants, NNT 1.8 (95% confidence interval 1.5 to 2.1)), ketoprofen gel (72% ketoprofen, 33% placebo, 5 studies, 348 participants, NNT 2.5 (2.0 to 3.4)), piroxicam gel (70% piroxicam, 47% placebo, 3 studies, 522 participants, NNT 4.4 (3.2 to 6.9)), diclofenac Flector plaster (63% Flector, 41% placebo, 4 studies, 1030 participants, NNT 4.7 (3.7 to 6.5)), and diclofenac other plaster (88% diclofenac plaster, 57% placebo, 3 studies, 474 participants, NNT 3.2 (2.6 to 4.2)). In chronic musculoskeletal pain (mainly hand and knee osteoarthritis) therapies were topical diclofenac preparations for less than six weeks (43% diclofenac, 23% placebo, 5 studies, 732 participants, NNT 5.0 (3.7 to 7.4)), ketoprofen over 6 to 12 weeks (63% ketoprofen, 48% placebo, 4 studies, 2573 participants, NNT 6.9 (5.4 to 9.3)), and topical diclofenac preparations over 6 to 12 weeks (60% diclofenac, 50% placebo, 4 studies, 2343 participants, NNT 9.8 (7.1 to 16)). In postherpetic neuralgia, topical high-concentration capsaicin had moderate-quality evidence of limited efficacy (33% capsaicin, 24% placebo, 2 studies, 571 participants, NNT 11 (6.1 to 62)). We judged evidence of efficacy for other therapies as low or very low quality. Limited evidence of efficacy, potentially subject to publication bias, existed for topical preparations of ibuprofen gels and creams, unspecified diclofenac formulations and diclofenac gel other than Emulgel, indomethacin, and ketoprofen plaster in acute pain conditions, and for salicylate Rubefacients for chronic pain conditions. Evidence for other interventions (other topical NSAIDs, topical salicylate in acute pain conditions, low concentration capsaicin, lidocaine, clonidine for neuropathic pain, and herbal remedies for any condition) was very low quality and typically limited to single studies or comparisons with sparse data. We assessed the evidence on withdrawals as moderate or very low quality, because of small numbers of events. In chronic pain conditions lack of efficacy withdrawals were lower with topical diclofenac (6%) than placebo (9%) (11 studies, 3455 participants, number needed to treat to prevent (NNTp) 26, moderate-quality evidence), and topical salicylate (2% vs 7% for placebo) (5 studies, 501 participants, NNTp 21, very low-quality evidence). Adverse event withdrawals were higher with topical capsaicin low-concentration (15%) than placebo (3%) (4 studies, 477 participants, NNH 8, very low-quality evidence), topical salicylate (5% vs 1% for placebo) (7 studies, 735 participants, NNH 26, very low-quality evidence), and topical diclofenac (5% vs 4% for placebo) (12 studies, 3552 participants, NNH 51, very low-quality evidence). In acute pain, systemic or local adverse event rates with topical NSAIDs (4.3%) were no greater than with topical placebo (4.6%) (42 studies, 6740 participants, high quality evidence). In chronic pain local adverse events with topical capsaicin low concentration (63%) were higher than topical placebo (5 studies, 557 participants, number needed to treat for harm (NNH) 2.6), high quality evidence. Moderate-quality evidence indicated more local adverse events than placebo in chronic pain conditions with topical diclofenac (NNH 16) and local pain with topical capsaicin high-concentration (NNH 16). There was moderate-quality evidence of no additional local adverse events with topical ketoprofen over topical placebo in chronic pain. Serious adverse events were rare (very low-quality evidence). GRADE assessments of moderate or low quality in some of the reviews were considered by us to be very low because of small numbers of participants and events. Authors' conclusions There is good evidence that some formulations of topical diclofenac and ketoprofen are useful in acute pain conditions such as sprains or strains, with low (good) NNT values. There is a strong message that the exact formulation used is critically important in acute conditions, and that might also apply to other pain conditions. In chronic musculoskeletal conditions with assessments over 6 to 12 weeks, topical diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis, as did topical high-concentration capsaicin in postherpetic neuralgia. Though NNTs were higher, this still indicates that a small proportion of people had good pain relief. Use of GRADE in Cochrane Reviews with small numbers of participants and events requires attention.
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salicylate containing Rubefacients for acute and chronic musculoskeletal pain in adults
Cochrane Database of Systematic Reviews, 2014Co-Authors: Sheena Derry, Paul M Matthews, Philip J Wiffen, Andrew R MooreAbstract:Background Rubefacients containing salicylates cause irritation of the skin and are believed to relieve various musculoskeletal pains. They are available on prescription, and are common components in over-the-counter remedies. This is an update of a review of Rubefacients for acute and chronic pain, originally published in 2009, which found limited evidence for efficacy. Objectives To assess the efficacy and safety of topically applied salicylates in acute and chronic musculoskeletal pain in adults. Search methods We searched CENTRAL, MEDLINE, and EMBASE, from inception to 22 August 2014, together with the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of included studies and relevant reviews. Selection criteria Randomised, double-blind, placebo- or active-controlled clinical trials of topical Rubefacients containing salicylates to treat musculoskeletal pain in adults, with at least 10 participants per treatment arm, and reporting outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14 (minimum 7) days or longer for chronic conditions. Data collection and analysis Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. We calculated risk ratio (RR) and number needed to treat to benefit or harm (NNT or NNH) with 95% confidence intervals (CI) using a fixed-effect model. We analysed acute and chronic conditions separately. Main results New searches for this update identified one new study that satisfied our inclusion criteria, although it contributed information only for withdrawals. Six placebo- and one active-controlled studies (560 and 137 participants, respectively) in acute pain, and seven placebo- and three active-controlled studies (489 and 182 participants, respectively) in chronic pain were included in the review. All studies were potentially at risk of bias, and there were substantial differences between studies in terms of the participants (for example the level of baseline pain), the treatments (different salicylates combined with various other potentially active ingredients), and the methods (for example the outcomes reported). Not all of the studies contributed usable information for all of the outcomes sought. For the primary outcome of clinical success at seven days in acute conditions (mostly sprains, strains, and acute low back pain), the RR was 1.9 (95% CI 1.5 to 2.5) and the NNT was 3.2 (2.4 to 4.9) for salicylates compared with placebo, but this result was not robust (very low quality evidence). Using a random-effects model for analysis the RR was 2.7 (1.05 to 7.0). For the same outcome in chronic conditions (mostly osteoarthritis, bursitis, and chronic back pain), the RR was 1.6 (1.2 to 2.0) and the NNT was 6.2 (4.0 to 13) (very low quality evidence). This result was not substantially changed using a random-effects model for analysis. In both categories there were a number of factors might have influenced the results but sensitivity analysis was limited because of the small number of studies and participants. For both acute and chronic painful conditions any evidence of efficacy came from the older, smaller studies, while the larger, more recent studies showed no effect. Adverse events were more common with salicylate than with placebo but most of the events occurred in only two studies. There was no difference when these studies were removed from the analysis (very low quality evidence). Local adverse events (at the application site) were again more common with salicylate but were nearly all in one study (in which salicylate was combined with another irritant). There was no difference when this study was removed (very low quality evidence). There were insufficient data to draw conclusions against active controls. Authors' conclusions The evidence does not support the use of topical Rubefacients containing salicylates for acute injuries or chronic conditions. They seem to be relatively well tolerated in the short-term, based on limited data. The amount and quality of the available data mean that uncertainty remains about the effects of salicylate-containing Rubefacients.
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systematic review of efficacy of topical Rubefacients containing salicylates for the treatment of acute and chronic pain
BMJ, 2004Co-Authors: Lorna Mason, Sheena Derry, Andrew R Moore, Jayne E Edwards, Henry J Mcquay, Philip J WiffenAbstract:Abstract Objective To determine the efficacy and safety of topical Rubefacients containing salicylates in acute and chronic pain. Data sources Electronic databases and manufacturers of salicylates. Study selection Randomised double blind trials comparing topical Rubefacients with placebo or another active treatment, in adults with acute or chronic pain, and reporting dichotomous information, around a 50% reduction in pain, and analyses at one week for acute conditions and two weeks for chronic conditions. Data extraction Relative benefit and number needed to treat, analysis of adverse events, and withdrawals. Data synthesis Three double blind placebo controlled trials had information on 182 patients with acute conditions. Topical salicylate was significantly better than placebo (relative benefit 3.6, 95% confidence interval 2.4 to 5.6; number needed to treat 2.1, 1.7 to 2.8). Six double blind placebo controlled trials had information on 429 patients with chronic conditions. Topical salicylate was significantly better than placebo (relative benefit 1.5, 1.3 to 1.9; number needed to treat 5.3, 3.6 to 10.2), but larger, more valid studies were without significant effect. Local adverse events and withdrawals were generally rare in trials that reported them. Conclusions Based on limited information, topically applied Rubefacients containing salicylates may be efficacious in the treatment of acute pain. Trials of musculoskeletal and arthritic pain suggested moderate to poor efficacy. Adverse events were rare in studies of acute pain and poorly reported in those of chronic pain. Efficacy estimates for Rubefacients are unreliable owing to a lack of good clinical trials.
Sheena Derry - One of the best experts on this subject based on the ideXlab platform.
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topical analgesics for acute and chronic pain in adults an overview of cochrane reviews
Cochrane Database of Systematic Reviews, 2017Co-Authors: Sheena Derry, Philip J Wiffen, Eija Kalso, Rae Frances Bell, Dominic Aldington, Tudor Phillips, Helen Gaskell, Andrew R MooreAbstract:Background Topical analgesic drugs are used for a variety of painful conditions. Some are acute, typically strains or sprains, tendinopathy, or muscle aches. Others are chronic, typically osteoarthritis of hand or knee, or neuropathic pain. Objectives To provide an overview of the analgesic efficacy and associated adverse events of topical analgesics (primarily nonsteroidal anti-inflammatory drugs (NSAIDs), salicylate Rubefacients, capsaicin, and lidocaine) applied to intact skin for the treatment of acute and chronic pain in adults. Methods We identified systematic reviews in acute and chronic pain published to February 2017 in the Cochrane Database of Systematic Reviews (the Cochrane Library). The primary outcome was at least 50% pain relief (participant-reported) at an appropriate duration. We extracted the number needed to treat for one additional beneficial outcome (NNT) for efficacy outcomes for each topical analgesic or formulation, and the number needed to treat for one additional harmful outcome (NNH) for adverse events. We also extracted information on withdrawals due to lack of efficacy or adverse events, systemic and local adverse events, and serious adverse events. We required information from at least 200 participants, in at least two studies. We judged that there was potential for publication bias if the addition of four studies of typical size (400 participants) with zero effect increased NNT compared with placebo to 10 (minimal clinical utility). We extracted GRADE assessment in the original papers, and made our own GRADE assessment. Main results Thirteen Cochrane Reviews (206 studies with around 30,700 participants) assessed the efficacy and harms from a range of topical analgesics applied to intact skin in a number of acute and chronic painful conditions. Reviews were overseen by several Review Groups, and concentrated on evidence comparing topical analgesic with topical placebo; comparisons of topical and oral analgesics were rare. For at least 50% pain relief, we considered evidence was moderate or high quality for several therapies, based on the underlying quality of studies and susceptibility to publication bias. In acute musculoskeletal pain (strains and sprains) with assessment at about seven days, therapies were diclofenac Emulgel (78% Emulgel, 20% placebo; 2 studies, 314 participants, NNT 1.8 (95% confidence interval 1.5 to 2.1)), ketoprofen gel (72% ketoprofen, 33% placebo, 5 studies, 348 participants, NNT 2.5 (2.0 to 3.4)), piroxicam gel (70% piroxicam, 47% placebo, 3 studies, 522 participants, NNT 4.4 (3.2 to 6.9)), diclofenac Flector plaster (63% Flector, 41% placebo, 4 studies, 1030 participants, NNT 4.7 (3.7 to 6.5)), and diclofenac other plaster (88% diclofenac plaster, 57% placebo, 3 studies, 474 participants, NNT 3.2 (2.6 to 4.2)). In chronic musculoskeletal pain (mainly hand and knee osteoarthritis) therapies were topical diclofenac preparations for less than six weeks (43% diclofenac, 23% placebo, 5 studies, 732 participants, NNT 5.0 (3.7 to 7.4)), ketoprofen over 6 to 12 weeks (63% ketoprofen, 48% placebo, 4 studies, 2573 participants, NNT 6.9 (5.4 to 9.3)), and topical diclofenac preparations over 6 to 12 weeks (60% diclofenac, 50% placebo, 4 studies, 2343 participants, NNT 9.8 (7.1 to 16)). In postherpetic neuralgia, topical high-concentration capsaicin had moderate-quality evidence of limited efficacy (33% capsaicin, 24% placebo, 2 studies, 571 participants, NNT 11 (6.1 to 62)). We judged evidence of efficacy for other therapies as low or very low quality. Limited evidence of efficacy, potentially subject to publication bias, existed for topical preparations of ibuprofen gels and creams, unspecified diclofenac formulations and diclofenac gel other than Emulgel, indomethacin, and ketoprofen plaster in acute pain conditions, and for salicylate Rubefacients for chronic pain conditions. Evidence for other interventions (other topical NSAIDs, topical salicylate in acute pain conditions, low concentration capsaicin, lidocaine, clonidine for neuropathic pain, and herbal remedies for any condition) was very low quality and typically limited to single studies or comparisons with sparse data. We assessed the evidence on withdrawals as moderate or very low quality, because of small numbers of events. In chronic pain conditions lack of efficacy withdrawals were lower with topical diclofenac (6%) than placebo (9%) (11 studies, 3455 participants, number needed to treat to prevent (NNTp) 26, moderate-quality evidence), and topical salicylate (2% vs 7% for placebo) (5 studies, 501 participants, NNTp 21, very low-quality evidence). Adverse event withdrawals were higher with topical capsaicin low-concentration (15%) than placebo (3%) (4 studies, 477 participants, NNH 8, very low-quality evidence), topical salicylate (5% vs 1% for placebo) (7 studies, 735 participants, NNH 26, very low-quality evidence), and topical diclofenac (5% vs 4% for placebo) (12 studies, 3552 participants, NNH 51, very low-quality evidence). In acute pain, systemic or local adverse event rates with topical NSAIDs (4.3%) were no greater than with topical placebo (4.6%) (42 studies, 6740 participants, high quality evidence). In chronic pain local adverse events with topical capsaicin low concentration (63%) were higher than topical placebo (5 studies, 557 participants, number needed to treat for harm (NNH) 2.6), high quality evidence. Moderate-quality evidence indicated more local adverse events than placebo in chronic pain conditions with topical diclofenac (NNH 16) and local pain with topical capsaicin high-concentration (NNH 16). There was moderate-quality evidence of no additional local adverse events with topical ketoprofen over topical placebo in chronic pain. Serious adverse events were rare (very low-quality evidence). GRADE assessments of moderate or low quality in some of the reviews were considered by us to be very low because of small numbers of participants and events. Authors' conclusions There is good evidence that some formulations of topical diclofenac and ketoprofen are useful in acute pain conditions such as sprains or strains, with low (good) NNT values. There is a strong message that the exact formulation used is critically important in acute conditions, and that might also apply to other pain conditions. In chronic musculoskeletal conditions with assessments over 6 to 12 weeks, topical diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis, as did topical high-concentration capsaicin in postherpetic neuralgia. Though NNTs were higher, this still indicates that a small proportion of people had good pain relief. Use of GRADE in Cochrane Reviews with small numbers of participants and events requires attention.
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salicylate containing Rubefacients for acute and chronic musculoskeletal pain in adults
Cochrane Database of Systematic Reviews, 2014Co-Authors: Sheena Derry, Paul M Matthews, Philip J Wiffen, Andrew R MooreAbstract:Background Rubefacients containing salicylates cause irritation of the skin and are believed to relieve various musculoskeletal pains. They are available on prescription, and are common components in over-the-counter remedies. This is an update of a review of Rubefacients for acute and chronic pain, originally published in 2009, which found limited evidence for efficacy. Objectives To assess the efficacy and safety of topically applied salicylates in acute and chronic musculoskeletal pain in adults. Search methods We searched CENTRAL, MEDLINE, and EMBASE, from inception to 22 August 2014, together with the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of included studies and relevant reviews. Selection criteria Randomised, double-blind, placebo- or active-controlled clinical trials of topical Rubefacients containing salicylates to treat musculoskeletal pain in adults, with at least 10 participants per treatment arm, and reporting outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14 (minimum 7) days or longer for chronic conditions. Data collection and analysis Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. We calculated risk ratio (RR) and number needed to treat to benefit or harm (NNT or NNH) with 95% confidence intervals (CI) using a fixed-effect model. We analysed acute and chronic conditions separately. Main results New searches for this update identified one new study that satisfied our inclusion criteria, although it contributed information only for withdrawals. Six placebo- and one active-controlled studies (560 and 137 participants, respectively) in acute pain, and seven placebo- and three active-controlled studies (489 and 182 participants, respectively) in chronic pain were included in the review. All studies were potentially at risk of bias, and there were substantial differences between studies in terms of the participants (for example the level of baseline pain), the treatments (different salicylates combined with various other potentially active ingredients), and the methods (for example the outcomes reported). Not all of the studies contributed usable information for all of the outcomes sought. For the primary outcome of clinical success at seven days in acute conditions (mostly sprains, strains, and acute low back pain), the RR was 1.9 (95% CI 1.5 to 2.5) and the NNT was 3.2 (2.4 to 4.9) for salicylates compared with placebo, but this result was not robust (very low quality evidence). Using a random-effects model for analysis the RR was 2.7 (1.05 to 7.0). For the same outcome in chronic conditions (mostly osteoarthritis, bursitis, and chronic back pain), the RR was 1.6 (1.2 to 2.0) and the NNT was 6.2 (4.0 to 13) (very low quality evidence). This result was not substantially changed using a random-effects model for analysis. In both categories there were a number of factors might have influenced the results but sensitivity analysis was limited because of the small number of studies and participants. For both acute and chronic painful conditions any evidence of efficacy came from the older, smaller studies, while the larger, more recent studies showed no effect. Adverse events were more common with salicylate than with placebo but most of the events occurred in only two studies. There was no difference when these studies were removed from the analysis (very low quality evidence). Local adverse events (at the application site) were again more common with salicylate but were nearly all in one study (in which salicylate was combined with another irritant). There was no difference when this study was removed (very low quality evidence). There were insufficient data to draw conclusions against active controls. Authors' conclusions The evidence does not support the use of topical Rubefacients containing salicylates for acute injuries or chronic conditions. They seem to be relatively well tolerated in the short-term, based on limited data. The amount and quality of the available data mean that uncertainty remains about the effects of salicylate-containing Rubefacients.
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systematic review of efficacy of topical Rubefacients containing salicylates for the treatment of acute and chronic pain
BMJ, 2004Co-Authors: Lorna Mason, Sheena Derry, Andrew R Moore, Jayne E Edwards, Henry J Mcquay, Philip J WiffenAbstract:Abstract Objective To determine the efficacy and safety of topical Rubefacients containing salicylates in acute and chronic pain. Data sources Electronic databases and manufacturers of salicylates. Study selection Randomised double blind trials comparing topical Rubefacients with placebo or another active treatment, in adults with acute or chronic pain, and reporting dichotomous information, around a 50% reduction in pain, and analyses at one week for acute conditions and two weeks for chronic conditions. Data extraction Relative benefit and number needed to treat, analysis of adverse events, and withdrawals. Data synthesis Three double blind placebo controlled trials had information on 182 patients with acute conditions. Topical salicylate was significantly better than placebo (relative benefit 3.6, 95% confidence interval 2.4 to 5.6; number needed to treat 2.1, 1.7 to 2.8). Six double blind placebo controlled trials had information on 429 patients with chronic conditions. Topical salicylate was significantly better than placebo (relative benefit 1.5, 1.3 to 1.9; number needed to treat 5.3, 3.6 to 10.2), but larger, more valid studies were without significant effect. Local adverse events and withdrawals were generally rare in trials that reported them. Conclusions Based on limited information, topically applied Rubefacients containing salicylates may be efficacious in the treatment of acute pain. Trials of musculoskeletal and arthritic pain suggested moderate to poor efficacy. Adverse events were rare in studies of acute pain and poorly reported in those of chronic pain. Efficacy estimates for Rubefacients are unreliable owing to a lack of good clinical trials.
Philip J Wiffen - One of the best experts on this subject based on the ideXlab platform.
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topical analgesics for acute and chronic pain in adults an overview of cochrane reviews
Cochrane Database of Systematic Reviews, 2017Co-Authors: Sheena Derry, Philip J Wiffen, Eija Kalso, Rae Frances Bell, Dominic Aldington, Tudor Phillips, Helen Gaskell, Andrew R MooreAbstract:Background Topical analgesic drugs are used for a variety of painful conditions. Some are acute, typically strains or sprains, tendinopathy, or muscle aches. Others are chronic, typically osteoarthritis of hand or knee, or neuropathic pain. Objectives To provide an overview of the analgesic efficacy and associated adverse events of topical analgesics (primarily nonsteroidal anti-inflammatory drugs (NSAIDs), salicylate Rubefacients, capsaicin, and lidocaine) applied to intact skin for the treatment of acute and chronic pain in adults. Methods We identified systematic reviews in acute and chronic pain published to February 2017 in the Cochrane Database of Systematic Reviews (the Cochrane Library). The primary outcome was at least 50% pain relief (participant-reported) at an appropriate duration. We extracted the number needed to treat for one additional beneficial outcome (NNT) for efficacy outcomes for each topical analgesic or formulation, and the number needed to treat for one additional harmful outcome (NNH) for adverse events. We also extracted information on withdrawals due to lack of efficacy or adverse events, systemic and local adverse events, and serious adverse events. We required information from at least 200 participants, in at least two studies. We judged that there was potential for publication bias if the addition of four studies of typical size (400 participants) with zero effect increased NNT compared with placebo to 10 (minimal clinical utility). We extracted GRADE assessment in the original papers, and made our own GRADE assessment. Main results Thirteen Cochrane Reviews (206 studies with around 30,700 participants) assessed the efficacy and harms from a range of topical analgesics applied to intact skin in a number of acute and chronic painful conditions. Reviews were overseen by several Review Groups, and concentrated on evidence comparing topical analgesic with topical placebo; comparisons of topical and oral analgesics were rare. For at least 50% pain relief, we considered evidence was moderate or high quality for several therapies, based on the underlying quality of studies and susceptibility to publication bias. In acute musculoskeletal pain (strains and sprains) with assessment at about seven days, therapies were diclofenac Emulgel (78% Emulgel, 20% placebo; 2 studies, 314 participants, NNT 1.8 (95% confidence interval 1.5 to 2.1)), ketoprofen gel (72% ketoprofen, 33% placebo, 5 studies, 348 participants, NNT 2.5 (2.0 to 3.4)), piroxicam gel (70% piroxicam, 47% placebo, 3 studies, 522 participants, NNT 4.4 (3.2 to 6.9)), diclofenac Flector plaster (63% Flector, 41% placebo, 4 studies, 1030 participants, NNT 4.7 (3.7 to 6.5)), and diclofenac other plaster (88% diclofenac plaster, 57% placebo, 3 studies, 474 participants, NNT 3.2 (2.6 to 4.2)). In chronic musculoskeletal pain (mainly hand and knee osteoarthritis) therapies were topical diclofenac preparations for less than six weeks (43% diclofenac, 23% placebo, 5 studies, 732 participants, NNT 5.0 (3.7 to 7.4)), ketoprofen over 6 to 12 weeks (63% ketoprofen, 48% placebo, 4 studies, 2573 participants, NNT 6.9 (5.4 to 9.3)), and topical diclofenac preparations over 6 to 12 weeks (60% diclofenac, 50% placebo, 4 studies, 2343 participants, NNT 9.8 (7.1 to 16)). In postherpetic neuralgia, topical high-concentration capsaicin had moderate-quality evidence of limited efficacy (33% capsaicin, 24% placebo, 2 studies, 571 participants, NNT 11 (6.1 to 62)). We judged evidence of efficacy for other therapies as low or very low quality. Limited evidence of efficacy, potentially subject to publication bias, existed for topical preparations of ibuprofen gels and creams, unspecified diclofenac formulations and diclofenac gel other than Emulgel, indomethacin, and ketoprofen plaster in acute pain conditions, and for salicylate Rubefacients for chronic pain conditions. Evidence for other interventions (other topical NSAIDs, topical salicylate in acute pain conditions, low concentration capsaicin, lidocaine, clonidine for neuropathic pain, and herbal remedies for any condition) was very low quality and typically limited to single studies or comparisons with sparse data. We assessed the evidence on withdrawals as moderate or very low quality, because of small numbers of events. In chronic pain conditions lack of efficacy withdrawals were lower with topical diclofenac (6%) than placebo (9%) (11 studies, 3455 participants, number needed to treat to prevent (NNTp) 26, moderate-quality evidence), and topical salicylate (2% vs 7% for placebo) (5 studies, 501 participants, NNTp 21, very low-quality evidence). Adverse event withdrawals were higher with topical capsaicin low-concentration (15%) than placebo (3%) (4 studies, 477 participants, NNH 8, very low-quality evidence), topical salicylate (5% vs 1% for placebo) (7 studies, 735 participants, NNH 26, very low-quality evidence), and topical diclofenac (5% vs 4% for placebo) (12 studies, 3552 participants, NNH 51, very low-quality evidence). In acute pain, systemic or local adverse event rates with topical NSAIDs (4.3%) were no greater than with topical placebo (4.6%) (42 studies, 6740 participants, high quality evidence). In chronic pain local adverse events with topical capsaicin low concentration (63%) were higher than topical placebo (5 studies, 557 participants, number needed to treat for harm (NNH) 2.6), high quality evidence. Moderate-quality evidence indicated more local adverse events than placebo in chronic pain conditions with topical diclofenac (NNH 16) and local pain with topical capsaicin high-concentration (NNH 16). There was moderate-quality evidence of no additional local adverse events with topical ketoprofen over topical placebo in chronic pain. Serious adverse events were rare (very low-quality evidence). GRADE assessments of moderate or low quality in some of the reviews were considered by us to be very low because of small numbers of participants and events. Authors' conclusions There is good evidence that some formulations of topical diclofenac and ketoprofen are useful in acute pain conditions such as sprains or strains, with low (good) NNT values. There is a strong message that the exact formulation used is critically important in acute conditions, and that might also apply to other pain conditions. In chronic musculoskeletal conditions with assessments over 6 to 12 weeks, topical diclofenac and ketoprofen had limited efficacy in hand and knee osteoarthritis, as did topical high-concentration capsaicin in postherpetic neuralgia. Though NNTs were higher, this still indicates that a small proportion of people had good pain relief. Use of GRADE in Cochrane Reviews with small numbers of participants and events requires attention.
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salicylate containing Rubefacients for acute and chronic musculoskeletal pain in adults
Cochrane Database of Systematic Reviews, 2014Co-Authors: Sheena Derry, Paul M Matthews, Philip J Wiffen, Andrew R MooreAbstract:Background Rubefacients containing salicylates cause irritation of the skin and are believed to relieve various musculoskeletal pains. They are available on prescription, and are common components in over-the-counter remedies. This is an update of a review of Rubefacients for acute and chronic pain, originally published in 2009, which found limited evidence for efficacy. Objectives To assess the efficacy and safety of topically applied salicylates in acute and chronic musculoskeletal pain in adults. Search methods We searched CENTRAL, MEDLINE, and EMBASE, from inception to 22 August 2014, together with the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of included studies and relevant reviews. Selection criteria Randomised, double-blind, placebo- or active-controlled clinical trials of topical Rubefacients containing salicylates to treat musculoskeletal pain in adults, with at least 10 participants per treatment arm, and reporting outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14 (minimum 7) days or longer for chronic conditions. Data collection and analysis Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. We calculated risk ratio (RR) and number needed to treat to benefit or harm (NNT or NNH) with 95% confidence intervals (CI) using a fixed-effect model. We analysed acute and chronic conditions separately. Main results New searches for this update identified one new study that satisfied our inclusion criteria, although it contributed information only for withdrawals. Six placebo- and one active-controlled studies (560 and 137 participants, respectively) in acute pain, and seven placebo- and three active-controlled studies (489 and 182 participants, respectively) in chronic pain were included in the review. All studies were potentially at risk of bias, and there were substantial differences between studies in terms of the participants (for example the level of baseline pain), the treatments (different salicylates combined with various other potentially active ingredients), and the methods (for example the outcomes reported). Not all of the studies contributed usable information for all of the outcomes sought. For the primary outcome of clinical success at seven days in acute conditions (mostly sprains, strains, and acute low back pain), the RR was 1.9 (95% CI 1.5 to 2.5) and the NNT was 3.2 (2.4 to 4.9) for salicylates compared with placebo, but this result was not robust (very low quality evidence). Using a random-effects model for analysis the RR was 2.7 (1.05 to 7.0). For the same outcome in chronic conditions (mostly osteoarthritis, bursitis, and chronic back pain), the RR was 1.6 (1.2 to 2.0) and the NNT was 6.2 (4.0 to 13) (very low quality evidence). This result was not substantially changed using a random-effects model for analysis. In both categories there were a number of factors might have influenced the results but sensitivity analysis was limited because of the small number of studies and participants. For both acute and chronic painful conditions any evidence of efficacy came from the older, smaller studies, while the larger, more recent studies showed no effect. Adverse events were more common with salicylate than with placebo but most of the events occurred in only two studies. There was no difference when these studies were removed from the analysis (very low quality evidence). Local adverse events (at the application site) were again more common with salicylate but were nearly all in one study (in which salicylate was combined with another irritant). There was no difference when this study was removed (very low quality evidence). There were insufficient data to draw conclusions against active controls. Authors' conclusions The evidence does not support the use of topical Rubefacients containing salicylates for acute injuries or chronic conditions. They seem to be relatively well tolerated in the short-term, based on limited data. The amount and quality of the available data mean that uncertainty remains about the effects of salicylate-containing Rubefacients.
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systematic review of efficacy of topical Rubefacients containing salicylates for the treatment of acute and chronic pain
BMJ, 2004Co-Authors: Lorna Mason, Sheena Derry, Andrew R Moore, Jayne E Edwards, Henry J Mcquay, Philip J WiffenAbstract:Abstract Objective To determine the efficacy and safety of topical Rubefacients containing salicylates in acute and chronic pain. Data sources Electronic databases and manufacturers of salicylates. Study selection Randomised double blind trials comparing topical Rubefacients with placebo or another active treatment, in adults with acute or chronic pain, and reporting dichotomous information, around a 50% reduction in pain, and analyses at one week for acute conditions and two weeks for chronic conditions. Data extraction Relative benefit and number needed to treat, analysis of adverse events, and withdrawals. Data synthesis Three double blind placebo controlled trials had information on 182 patients with acute conditions. Topical salicylate was significantly better than placebo (relative benefit 3.6, 95% confidence interval 2.4 to 5.6; number needed to treat 2.1, 1.7 to 2.8). Six double blind placebo controlled trials had information on 429 patients with chronic conditions. Topical salicylate was significantly better than placebo (relative benefit 1.5, 1.3 to 1.9; number needed to treat 5.3, 3.6 to 10.2), but larger, more valid studies were without significant effect. Local adverse events and withdrawals were generally rare in trials that reported them. Conclusions Based on limited information, topically applied Rubefacients containing salicylates may be efficacious in the treatment of acute pain. Trials of musculoskeletal and arthritic pain suggested moderate to poor efficacy. Adverse events were rare in studies of acute pain and poorly reported in those of chronic pain. Efficacy estimates for Rubefacients are unreliable owing to a lack of good clinical trials.
Karin Jacobs - One of the best experts on this subject based on the ideXlab platform.
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A phylogenetic revision of Penicillium sect. Exilicaulis, including nine new species from fynbos in South Africa
IMA Fungus, 2016Co-Authors: Cobus M. Visagie, Keith A. Seifert, Jos Houbraken, Robert A. Samson, Karin JacobsAbstract:A survey of the fynbos biome in South Africa resulted in the isolation of 61 Penicillium species from Protea repens infructescences, air, and soil samples. Fourteen of these belong to Penicillium sect. Exilicaulis and therefore we considered it an opportunity to re-evaluate the taxonomy of the section. Phylogenetic comparisons of the ITS, β-tubulin, calmodulin and RPB2 gene regions of the 76 section Exilicaulis species, revealed 52 distinct species, including nine new species from fynbos. Morphological comparisons confirmed the novelty for most of these, however, new species closely related to P rubefaciens did not show significant or consistent morphological differences and we thus placed a bias on phylogenetic data applying the Genealogical Concordance Phylogenetic Species Recognition (GCPSR) concept. In this paper we describe the nine new species and update the accepted species list and resolve synonyms in the section. Importantly, we reveal that P. citreosulfuratum is the correct name for the clade previously considered to represent P. toxicarium fide Serra et al . (2008). The nine new species are: Penicillium atrolazulinum, P consobrinum, P cravenianum, P. hemitrachum, P pagulum, P repensicola, P momoii, P subturcoseum , and P xanthomelinii spp. nov.
Juan Santiago Cortizas-rey - One of the best experts on this subject based on the ideXlab platform.
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Revisión histórica sobre el uso en heridas del emplasto confortativo de Vigo
2017Co-Authors: José María Rumbo-prieto, Alba Cortizas-montero, Juan Santiago Cortizas-reyAbstract:Resumen: Objetivo: Dar a conocer el origen, la elaboración e indicación terapéutica del denominado “emplasto confortativo de Vigo”. Método: Estudio descriptivo hermenéutico de revisión histórica y documental. Lectura crítica de manuales y tratados médicos, farmacopeas y otros textos científicos desde el siglo XVII al XIX. Exposición de resultados de forma narrativa. Resultados: Juan de Vigo fue un médico-cirujano genovés de finales del siglo XVI, que experimentó con diferentes ungüentos y emplastos, entre los que destacó los mercuriales y uno a base de minio (polvo rojo de plomo) combinado con trementina (resina de pino); muy popular y efectivo por su acción Rubefaciente, astringente, emoliente y resolutiva. Fue conocido oficialmente en la farmacopea española como “emplasto confortativo (de Vigo)”. Conclusiones: El emplasto Conformativo de Vigo aparece en todas las ediciones de la farmacopea española como tratamiento de primera elección para calmar dolencias óseo-articulares y diversas úlceras pustulosas, atónicas y recalcitrantes. Su elaboración sirvió de base para crear más de 20 tipos de emplastes. Dejaría de usarse a mediados del siglo XX, cuando se prohibió en España utilizar medicamentos combinados con plomo. Abstract: Objective: To present the origin, the elaboration and therapeutic indication of the so-called "confortative poultice of Vigo". Method: Hermeneutic descriptive study of historical and documentary review. Critical reading of manuals and medical treatises, pharmacopoeias and other scientific texts from the seventeenth to the nineteenth century. Exhibition of results in narrative form. Results: Juan de Vigo was a Genoese doctor-surgeon of the late sixteenth century, who experimented with different ointments and plasters, among which the mercurials and one based on minium (red lead powder) combined with turpentine (pine resin). ); very popular and effective for its Rubefaciente, astringent, emollient and resolutive action. It was officially known in the Spanish pharmacopoeia as "comforting poultice (of Vigo)". Conclusions: The Conformativo de Vigo poultice appears in all editions of the Spanish pharmacopoeia as the first-line treatment to relieve osseous-articular ailments and various pustular, atonic and recalcitrant ulcers. Its development served as the basis to create more than 20 types of plasters. It would cease to be used in the mid-twentieth century, when it was banned in Spain to use drugs combined with lead
